CNTN2 p.Ala596=
c.1788G>A · rs151320977 · VCV1650701
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0134%, afr)
Conditions
1
epilepsy, familial adult myoclonic, 5
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -6.4 | GERP -4.9 |
| Overall | ||
| CADD | 3.287 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0134%
African / African-American · 10/74,772 alleles
Filtering AF
0.00724%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00551%
Overall
0.00161%
26/1,612,448 alleles · ultra-rare
exomes 21/1,461,034 · genomes 5/151,414 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.0134% | 7,477 |
| Admixed American | 0.00668% | 14,965 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,426 |
| European (non-Finnish) | 0.000933% | 107,200 |
Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.
Variant & gene context
- Gene
- CNTN2
- Protein
- p.Ala596=
- Coding
- c.1788G>A
- MANE Select
- NM_005076
- dbSNP
- rs151320977
- Type
- single nucleotide variant
- Location
- chr1:205065881 (GRCh38)
- Gene constraint
- LOEUF 0.542 · pLI 0.02 (gnomAD)
- Structure
- AlphaFold pLDDT 86.13 · 5 PDB
- Residue 596
- a β-strand; the ig-like c2-type 6 domain
Similar variants
- CNTN2 p.Ala596Val Uncertain significance ★★ ⚠ same residue
- CNTN2 p.Ala596Thr Conflicting classifications of pathogenicity ★ ⚠ same residue
- CNTN2 c.1241-1G>C Likely pathogenic ★★ same condition
- CNTN2 c.2432-2A>G Likely pathogenic ★★ same condition
- CNTN2 p.Arg140Ter Pathogenic/Likely pathogenic ★★ same condition
- CNTN2 p.Arg314Ter Pathogenic ★★ same condition
- CNTN2 p.Trp731Ter Pathogenic/Likely pathogenic ★★ same condition
- CNTN2 c.2196+5G>A Uncertain significance ★★ same condition
Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →
Cite Sugi Variant
Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/cntn2-p-ala596 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown